Abstract
Hydrogel materials have been employed as biological scaffolds for tissue regeneration across a wide range of applications. Their versatility and biomimetic properties make them an optimal choice for treating the complex and delicate milieu of neural tissue damage. Aside from finely tailored hydrogel properties, which aim to mimic healthy physiological tissue, a minimally invasive delivery method is essential to prevent off-target and surgery-related complications. The specific class of injectable hydrogels termed self-assembling peptides (SAPs), provide an ideal combination of in situ polymerization combined with versatility for biofunctionlization, tunable physicochemical properties, and high cytocompatibility. This review identifies design criteria for neural scaffolds based upon key cellular interactions with the neural extracellular matrix (ECM), with emphasis on aspects that are reproducible in a biomaterial environment. Examples of the most recent SAPs and modification methods are presented, with a focus on biological, mechanical, and topographical cues. Furthermore, SAP electrical properties and methods to provide appropriate electrical and electrochemical cues are widely discussed, in light of the endogenous electrical activity of neural tissue as well as the clinical effectiveness of stimulation treatments. Recent applications of SAP materials in neural repair and electrical stimulation therapies are highlighted, identifying research gaps in the field of hydrogels for neural regeneration.
Highlights
Neural tissue loss represents a complex clinical challenge, which translates to a heavy burden for society
This review examines the recent developments in self-assembling peptides (SAPs) systems designed for neural applications, including methods to tailor SAP properties to optimize their performance as neural scaffolds which can guide neural repair
Aligned topography is found to be among the most effective in neural tissue regeneration, due to their polarized morphology, which mimics physiological patterns in neural tissue.[28,32,63,93,143,160−163] Human neural stem cell (NSC) are shown to differentiate toward the neuronal lineage when exposed to aligned microscale patterns, and neurite outgrowth can be enhanced by contact guidance.[93,145,164−166] For example, dorsal root ganglia cells increase the maximum length of their neurites by 82% when exposed to core−sheath nanofibers.[167]
Summary
Neural tissue loss represents a complex clinical challenge, which translates to a heavy burden for society. The overarching aim of tissue engineering scaffolds is to use a material system to mimic the physicochemical properties of the natural tissue milieu.[18,19] Biomimetic scaffolds, made from biologically inspired materials, provide environmental cues that target desired biological mechanisms.[20,21,254] Such biomimetic cues can be used to control cell and tissue behavior, promoting neural tissue regeneration and repair These elements can take the form of bioactive molecules and pharmaceuticals, as well as mechanical and topographical cues for physical support.[6] These tissue scaffold materials need to be carefully designed. The latest SAP-based applications for neural regeneration are presented, to identify their advantages and limitations, highlighting the latest technological advances and unmet clinical needs
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